21-44286017-ACG-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000383.4(AIRE):c.14_15delCG(p.Ala5GlyfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000383.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AIRE | ENST00000291582.6 | c.14_15delCG | p.Ala5GlyfsTer29 | frameshift_variant | Exon 1 of 14 | 1 | NM_000383.4 | ENSP00000291582.5 | ||
AIRE | ENST00000527919.5 | n.175_176delCG | non_coding_transcript_exon_variant | Exon 1 of 14 | 2 | |||||
AIRE | ENST00000530812.5 | n.183_184delCG | non_coding_transcript_exon_variant | Exon 1 of 12 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Polyglandular autoimmune syndrome, type 1 Pathogenic:1
This sequence change creates a premature translational stop signal (p.Ala5Glyfs*29) in the AIRE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AIRE are known to be pathogenic (PMID: 11524731, 26141571). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.